Prevalence and Impact of Psychological Disorders on Pharmacotherapy of Diabetic Patients in Low Resource Settings: A Prospective Assessment in Primary Healthcare Settings

Introduction

Individuals with diabetes face a twofold increased likelihood of being diagnosed with depression compared to the general population.¹ In recent decades, there has been a global increase in the prevalence of diabetes among adults.² According to IDF, the global prevalence of diabetes was estimated to be around 536.6 million in the year 2021. This figure is expected to undergo a substantial increase, reaching approximately 783.2 million by the year 2045.³ Pakistan holds third global ranking in terms of diabetes prevalence.⁴

The prevalence of psychological disorders among patients with diabetes is greater than that observed in the general population.⁵ Depression impacts roughly one in every five diabetes patients. This prevalence is around three times higher than the anticipated rate of depression in the general population.⁶ Some studies suggest that around 40% of patients with diabetes experience elevated levels of depressive symptoms.⁶ The Prevalence of psychiatric disorders in Pakistan is much higher in comparison to western countries.⁷

Despite the high prevalence of depression in individuals with diabetes, it often remains undiagnosed, and only one-third of depressed diabetic patients receive a diagnosis and treatment.⁸ Depression and type-2 diabetes may also have common biological basis.⁵ Meta-analyses of the available literature have demonstrated a consistent relationship between depression and hyperglycemia,⁹ an elevated risk of diabetes complications,¹⁰ non-adherence to diabetes therapy¹¹ and increased risk of deaths.^12,13

Depression also influence the progression of diabetes and has been associated with inadequate self-management,¹⁴ failure to attain clinical goals,¹⁵ contributes to an increased burden of diabetes symptoms,¹⁶ reduced quality of life,¹⁷ high economic burden,¹⁸ increased number of missed doses of diabetic medications^19,20 and perceived functional limitation of diabetes.²¹

Existence of depressive symptoms has also been identified as a potential factor linked to inadequate glycemic control.⁹ Poor glycemic control, in turn, increases the risk of developing complications like stroke, cardiovascular incidents, amputation, and chronic kidney disease among individuals with diabetes.²²

In Pakistan, patient with diabetes and depression exhibit significantly poor glycemic control, likely due to lower adherence to recommended self-care activities. Patients with longer illness duration and diabetes related complications, reported inadequate adherence to prescribed medication therapy, which correlated with poor glycemic control.²³ Many diabetes patients in Pakistan also lack essential information necessary to improve medication adherence due to limited access to health care providers.²⁴

In Pakistan, the National Action Plan for Non-Communicable Diseases Prevention and Control emphasizes prevention and management but lacks implementation, particularly at primary healthcare facilities. Rural health centers and sub-district hospitals lack standard guidelines and resources for diabetes care, with specialist only available at district level hospitals. The referral system is weak, leading to inadequate diabetes management and care for associated complications.²⁵

Collaborative care is also uncommon in Pakistani healthcare system, with limited physician-pharmacist interaction in designing therapeutic regimes and barriers to pharmacists providing clinical services. Consequently, diabetes patients often lack necessary education to improve medication adherence.²⁴

High prevalence of psychological disorder in diabetic patients not only disrupts glucose metabolism but also impacts behavioral risk factors including insufficient physical activity and the consumption of high calorie diets which contribute to obesity and further exacerbate glucose-related issues.²⁰ Limited reports are available that highlight the existence of psychological disorders in diabetic population and associated relationship between psychological disorders and pharmacotherapy in diabetic patients. Most studies on depression among people with diabetes were conducted in specialized diabetes care centers. To our knowledge, few studies have examined the prevalence and impact of depression in diabetics in rural center. Therefore, this study was designed to assess the prevalence and impact of depression on the pharmacotherapy of diabetic patients. This study will provide valuable insight for diabetologist and allied health professionals to include direct monitoring of diabetic patients with depression at resource limited healthcare settings.

Aim

This study aimed to assess the prevalence and impact of psychological disorders on pharmacotherapy of diabetes patients.

Ethics Approval

Ethical approval was taken from the Chairman of the Bioethics Committee at the University of the Punjab, Lahore (Reference No. 3265). Additionally, we obtained permission to carry out the study from THQ Hospital Pasrur (NO.HR/1457/THQ/PSR), and from THQ Hospital Daska (No. 3765/E. I). The PHQ-9 questionnaire was adopted after the necessary permission from the principal author. Permission to use the PHQ-9 scale was sought from the principal author via email, and the acknowledgeable response confirmed that the scale is now accessible in public domain for non-commercial research purpose. Therefore, the study complies with the Declaration of Helsinki.

Methodology

Study Design and Setting

The study design was observational cross sectional study. The methodology adopted for the conduct of this study followed the Equator’s checklist of observational studies. STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines were followed to conduct the current study. The study was undertaken at two primary healthcare settings of Punjab province of Pakistan including Tehsil Headquarter Hospital Pasrur and Tehsil Headquarter Hospital Daska (70 and 150 bedded hospitals respectively) from April to June 2023.

Inclusion and Exclusion Criteria

The patients who were enrolled at the non-communicable disease (NCD) centers of above two hospitals for the management and follow-up of type-2 diabetes mellitus (BSR value greater than 200mg/dl) approached from vicinity of these hospitals in Out Patient Doors (OPDs) were enrolled. Patients aged 18 years or above, diagnosed of having type-2 diabetes mellitus (prior to their visit to the diabetes outpatient facility) were included. Pregnant women and anyone deemed seriously ill by the care taking medical professional were excluded from the study.

Study Variables

Demographic details and treatment-related information were collected from patients on a pre-designed validated questionnaire. The demography included parameters such as age, gender, educational background, income level, residential location (urban or rural), diabetes history, duration of the disease, family history of diabetes, blood sugar random (BSR) value, number of hospital admissions, and any diabetes-related complications. The Pharmacotherapy variables included parameters such as adherence, any side effect experienced, modification to diabetes treatment plan and number of missed doses.

Psychological disorders were assessed using the Patient Health Questionnaire-9 (PHQ-9) scale. The PHQ-9 questionnaire is a validated tool consisting of nine items, each corresponding to one of the nine depression criteria outlined in the DSM-IV. These nine items of questionnaire address aspects such as lack of interest or pleasure in activities, feeling of hopelessness, sleep disturbances, fatigue, change in appetite, negative self-perception, difficulty concentrating, physical restlessness and suicidal ideation.

Data Collection Tool and Procedure

A data collection form was designed to gather demographic information and diabetes-specific history from patients and the data was collected through face-to-face interviews.

Patients were asked to recall any depressive symptoms they experienced over the preceding 2 weeks and provide responses on a four-point Likert scale, ranging from 0 (not at all) to 3 (nearly every day). When compared to structured interviews by mental health professionals, a PHQ-9 score of ≥10 was identified as the most effective threshold for diagnosing major depression, demonstrating both high sensitivity and specificity at 88%.²⁶ A cut of point of greater than 10 is also optimal for epidemiological research as it includes a broader range of participants, who may have depressive disorders, ensuring a more comprehensive representation of the population potential’s depression severity.²⁷ The PHQ-9 is widely recognized as one of the most commonly used depression screening instruments, particularly in primary care settings.

Patients who scored 10 or higher on the PHQ-9 questionnaire were further asked about their psychological disorder treatment. Those individuals who had been prescribed medication for psychological disorders were interviewed in detail regarding how these disorders affected their blood glucose levels, diabetes treatment plan, adherence to treatment, instances of missed doses, and any encountered side effects. This comprehensive evaluation aimed to assess the impact of psychological disorders on the pharmacotherapy of diabetic patients.

Patients may inaccurately recall their medical history and potentially under-report or over report psychological symptoms. To minimize this bias, the study employed a rigorous data collection approach. Data were exclusively collected by two trained interviewers and a validated questionnaire tool was employed to accurately assess the presence and severity of depressive symptoms.

Sample Size

The study employed a non-probability convenience sampling technique. The sample size was calculated using Raosoft formula taking 95% level of confidence and + 05% margin of error. Using this formula, we have calculated minimum sample size as 320 patients. The study included all the diabetic patients who visited NCD (non-communicable Disease) clinic of selected primary healthcare hospitals. All the participants were elaborated regarding the purpose of study prior to the conduct. Figure 1 shows a flow chart scheme of study population and final recruited patients.

Figure 1 A flow chart showing scheme of study population and final recruited patients. Abbreviations: *NCD, Non-communicable disease; ICU, Intensive care unit.

Data Analysis

Data analysis was carried out using the IBM SPSS Statistics version 27.0. Simple descriptive statistics was applied on demographic variables. Chi-square test was used to assess the relationship between ordinal variables/categorical variables and depression whereas; Student’s t-test was used to assess the relationship between numerical variables with depression. A p-value ≤0.05 was considered statistically significant.

Results

A total of 320 patients (200 females, 120 males) with average age 52.48 (SD±11.76) years were included in the study. The maximum participants were female (62.5%). The average duration of diabetes is 7.03 (SD±5.39) The majority of patients 30.6% (n=98) were suffering from the illness for 1–5 years’ duration and most of the patients 40.3% (n=129) had blood sugar level (BSR value) greater than 125 mg/dl while 32.8% (n=105) of the patients had blood sugar random (BSR value) greater than 300mg/dl. The 71.3% (n=228) participants manage their diabetes using injectable insulin,17.8% (n=57) individual uses oral hypoglycemic agents and 6.6% (n=21) individual uses Insulin + oral hypoglycemic agents (Table 1).

Table 1 Demographic Characteristics of Participants and Relevant Variables

The prevalence of psychological disorders specifically depression was 43.7%, using the commonly accepted cut-off value of 10. The distribution of PHQ-9 severity cut-off values was as follows: none/minimal depression 33.1% (n=106), mild 23.1% (n=74), moderate 28.1% (n=90), moderately severe 13.1% (n=42), and severe 2.5% (n=08). Figure 2 details the prevalence of disorders.

Figure 2 Frequency of depression severity among study participants.

Table 2 describes the impact of various variables on the occurrence of depression (Table 2). A significant correlation between gender and the prevalence of depression, with women being more commonly affected by depression than men (p-value = 0.005). Furthermore, individuals with a diabetes duration exceeding 10 years’ have higher BSR value (greater than 300) and were found to be at a higher risk of experiencing depression when compared to those who have controlled diabetes (P-value; <0.001).

Table 2 Effect of Demographic Variables on Psychological Disorders

Individual who has BSR value greater than 300 also most commonly suffer from comorbid diseases/diabetes related complications, consequently increasing their susceptibility to depression (P-value; <0.001). Patients who administer injectable insulin twice daily had also significant level of depression as compared to the patient who use oral hypoglycemic agents to control/manage their diabetes.

Among the total number of individuals (320) in the study, a notable 43.7% experienced symptoms of depression. Only a small proportion, just 11.3% of the study individuals, were formally diagnosed with depression and subsequently prescribed anti-depressants for its management.

A statistically significant association was found between depression and treatment adherence. Approximately 7.5% (n=24) of the study individuals reported experiencing difficulties in strictly adhering to their prescribed diabetes treatment regime. There is also a significant correlation identified between number of missed doses in diabetes treatment and the presence of depression, as 3.8% (n=12) indicated a specific number of missed doses. About 8.1% (n=26) of these patients felt that their psychological disorders had a tangible effect on their ability to manage their diabetes appropriately. Table 3 shows data about the effect of psychological disorders on pharmacotherapy of diabetes.

Table 3 Effect of Psychological Disorders on Pharmacotherapy of Diabetic Patients

Discussion

The rising global prevalence of diabetes has exacerbated the challenge of managing this chronic condition, particularly due to the frequent occurrence of psychological issues in this population. To address this concern, our study was carried out within the Pakistani population to determine the prevalence and impact of depression among individuals with diabetes mellitus and to assess the effect of depression on the pharmacotherapy of diabetic patients.

Our findings revealed a significant prevalence of depression, affecting approximately 43.7% of the study participants. These results are consistent with previous research conducted in Pakistan and other regions.

The findings of a study conducted in Pakistan on the prevalence of depression among diabetic patients reports depression prevalence rate of about 40%,²⁸ While a similar study in Karachi, reported 43.5%.²⁹ In South Africa, a semi-rural clinic study found that 45.9% of individuals with diabetes were experiencing depression.³⁰ In Iran, another study reported a prevalence of 47.6%³¹ and a study by Thour et al found a 41% prevalence.³² The variability in depression prevalence across studies can be attributed to factors including variation in screening scale used to assess symptoms and diverse settings.

Our study revealed that females were more commonly affected by depression than males, this finding aligns with studies conducted in previous studies undertaken in United States.³³ Researchers have also found significant relationship between age and depression.³⁴ This is in line with our study findings that also revealed that increased age as an independent risk factor for depression. The study also revealed a connection between depression and low educational attainment and income levels, which corresponds with findings in previous studies.^35,36

Our study identified a correlation between the duration of diabetes and the development of depression, aligning with findings from other research studies.^34,37 Poor glycemic control was also strongly linked to depression in our results. This finding is in line with previous research studies conducted in America.³⁸

Our study also found a significant relationship between the presence of other chronic conditions, such as hypertension or asthma, and an elevated risk of depression aligning with previous research.³⁹ Additionally, presence of complications like nephropathy, neuropathy, and diabetic foot along with other comorbid conditions can significantly raise the risk of developing of depression. The development of depression can also be influenced by functional limitations stemming from complications like retinopathy and amputation.⁴⁰

A significant correlation was also found between the frequency of hospital admissions due to diabetes-related complications and the presence of depression, consistent with earlier research indicating higher rates of anxiety and depression among hospitalized individuals.^41,42

We also observed that patients using insulin or a combination of insulin and oral hypoglycemic agents exhibited higher rates of depression in comparison to those who were solely relying on oral hypoglycemic agents, consistent with previous research.^43,44

Results of our study revealed that patients with depression had significantly lower adherence to diabetes medication therapy compared to patients without depression. These findings align with previous studies, indicating that individual with diabetes and depression tend to have poorer medication adherence.¹⁹ Consistently, other research has shown that individuals with elevated depressive symptom scores tend to exhibit lower adherence to their diabetes medication regimens in comparison to those with lower depressive symptom scores.^45,46

Depression also raises the frequency of missed doses. Similar findings were observed in another study, where depression was linked to memory loss. This association may cause people to forget to take their medications on time.⁴⁷

The findings of our study emphasize the importance of assessing depression as a fundamental component of evaluating diabetic patients, aligning with recommendations from the American Diabetic Association that advocates for the screening and assessment of depression in all individuals with type 2 diabetes mellitus.⁴⁸ Furthermore, our study highlights the crucial role of diabetic educators in offering guidance and education to individuals with diabetes. They play a vital role in dispelling myths and addressing false beliefs related to diabetes management, especially in resource-limited settings. It is crucial to make sure that people with depression are promptly sent to psychiatrists for counselling and therapy. This proactive approach is essential in preventing a vicious loop where non-compliance with anti-diabetic medications leads to poor diabetes control, which, in turn, exacerbates depression. Collaborative care and support from healthcare professionals in both diabetes and mental health fields are essential to improve overall health outcomes for individuals with diabetes and depression.²⁸ Integrated care approaches could potentially alleviate the challenges faced by diabetic patients with depression and improve their quality of life.

Strength and Limitation

The strength of our study include a manageable sample size, high response rate and its inclusivity, which allowed participants of all literacy levels to participate.³⁶

Our study has also some limitations as well. Firstly, the absence of a control group for comparison. Secondly, we utilized the patient health questionnaire (PHQ-9) to measure depression at a single point in time, lacking of follow up data. Thirdly, we focused on a specific subset of individuals diagnosed with psychological disorder. So, our interviews regarding adherence to diabetes medication and instance of missed doses were only conducted with this restricted cohort and the investigation was only carried out in two government hospitals, which limits the ability to generalize study findings.

Conclusions

This study highlights a high prevalence of depression in diabetic population. A culminating strong association was assessed between diabetes and depression. Furthermore, it is observed that depression exacerbates the therapy of diabetes, contributing to poorly controlled diabetes and subsequent complications. Finally, the psychological disorders hinder adherence to diabetes medication, consequently intensifying the challenges associated with diabetes management.

Future Research and Recommendations

Routine monitoring of diabetic patients with depression in primary care settings is strongly recommended to enable early detection and timely intervention. Specialized training for diabetic educators is essential to effectively support patients dealing with both diabetes and depression. More importantly, patients should be educated about the bidirectional relationship between diabetes and depression, emphasizing the importance of managing both conditions together. Furthermore, continuous research into innovative interventions, treatments, and technologies is crucial for optimizing the management of diabetes and depression together.

Impact Statements

• Data from low resourced settings substantiate a significant relationship between depression and diabetes. Alarmingly, untreated psychological disorders impact the pharmacotherapy of diabetes.
• There is a dire need to develop integrated strategies to address both conditions simultaneously.
• It is imperative to initiate specialized programmes for personalized care of diabetic-depression comorbid population and relevant skill development of dealing healthcare professionals.